Pedro F. Vale

Temperature-dependent costs of parasitism and maintenance of polymorphism under genotype-by-environment interactions.

The maintenance of genetic variation for infection‐related traits is often attributed to coevolution between hosts and parasites, but it can also be maintained by environmental variation if the relative fitness of different genotypes changes with environmental variation. To gain insight into how infection‐related traits are sensitive to environmental variation, we exposed a single host genotype of the freshwater crustacean Daphnia magna to four parasite isolates (which we assume to represent different genotypes) of its naturally co‐occurring parasite Pasteuria ramosa at 15, 20 and 25 °C. We found that the cost to the host of becoming infected varied with temperature, but the magnitude of this cost did not depend on the parasite isolate. Temperature influenced parasite fitness traits; we found parasite genotype‐by‐environment (G × E) interactions for parasite transmission stage production, suggesting the potential for temperature variation to maintain genetic variation in this trait. Finally, we tested for temperature‐dependent relationships between host and parasite fitness traits that form a key component of models of virulence evolution, and we found them to be stable across temperatures.

CRISPR-mediated phage resistance and the ghost of coevolution past

The past is never dead. Its not even past William Faulkner (1951) Bacteria can acquire heritable immunity to viral (phage) enemies by incorporating phage DNA into their own genome. This mechanism of anti-viral defence, known by the acronym CRISPR, simultaneously stores detailed information about current and past enemies and the evolved resistance to them. As a high-resolution genetic marker that is intimately tied with the host–pathogen interaction, the CRISPR system offers a unique, and relatively untapped, opportunity to study epidemiological and coevolutionary dynamics in microbial communities that were previously neglected because they could not be cultured in the laboratory. We briefly review the molecular mechanisms of CRISPR-mediated host–pathogen resistance, before assessing their potential importance for coevolution in nature, and their utility as a means of studying coevolutionary dynamics through metagenomics and laboratory experimentation.

Epidemiological, Evolutionary, and Coevolutionary Implications of Context-Dependent Parasitism

Victims of infection are expected to suffer increasingly as parasite population growth increases. Yet, under some conditions, faster-growing parasites do not appear to cause more damage, and infections can be quite tolerable. We studied these conditions by assessing how the relationship between parasite population growth and host health is sensitive to environmental variation. In experimental infections of the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we show how easily an interaction can shift from a severe interaction, that is, when host fitness declines substantially with each unit of parasite growth, to a tolerable relationship by changing only simple environmental variables: temperature and food availability. We explored the evolutionary and epidemiological implications of such a shift by modeling pathogen evolution and disease spread under different levels of infection severity and found that environmental shifts that promote tolerance ultimately result in populations harboring more parasitized individuals. We also find that the opportunity for selection, as indicated by the variance around traits, varied considerably with the environmental treatment. Thus, our results suggest two mechanisms that could underlie coevolutionary hotspots and coldspots: spatial variation in tolerance and spatial variation in the opportunity for selection.

Measuring parasite fitness under genetic and thermal variation

Accurate measures of parasite fitness are essential to study host–parasite evolution. Parasite fitness depends on several traits involved in establishing infection, growth and transmission. Individually, these traits provide a reasonable approximation of fitness, but they may also be under the shared control of both host and parasite genetics (GH × GP interactions), or be differentially sensitive to environmental variation. Using the natural host–parasite system Daphnia magna–Pasteuria ramosa, we performed experimental infections that incorporated host and parasite genetic variation at three different temperatures, and compared the measures of parasite fitness based only on growth rate, or incorporating the ability to infect. We found that infectivity was most important for parasite fitness and depended mainly on the combination of host and parasite genotypes. Variation in post-infection parasite growth and killing time depended on the parasite genotype and its interaction with temperature. These results highlight the merits of studies that can incorporate natural infection routes and emphasize that accurate measures of parasite fitness require knowledge of the genetic control and environmental sensitivity of more than one trait. In addition, no GH × GP × E interactions were present, suggesting that the potential for genetic specificities to drive frequency-dependent coevolution in this system is robust to thermal variation.

Co-infection alters population dynamics of infectious disease

Co-infections by multiple pathogen strains are common in the wild. Theory predicts co-infections to have major consequences for both within- and between-host disease dynamics, but data are currently scarce. Here, using common garden populations of Plantago lanceolata infected by two strains of the pathogen Podosphaera plantaginis, either singly or under co-infection, we find the highest disease prevalence in co-infected treatments both at the host genotype and population levels. A spore-trapping experiment demonstrates that co-infected hosts shed more transmission propagules than singly infected hosts, thereby explaining the observed change in epidemiological dynamics. Our experimental findings are confirmed in natural pathogen populations—more devastating epidemics were measured in populations with higher levels of co-infection. Jointly, our results confirm the predictions made by theoretical and experimental studies for the potential of co-infection to alter disease dynamics across a large host–pathogen metapopulation.

Limiting Damage during Infection: Lessons from Infection Tolerance for Novel Therapeutics

In the field of infectious disease control, novel therapies are focusing on reducing illness caused by pathogens rather than on reducing the pathogen burden itself. Here, Vale and colleagues highlight some potential consequences of such therapeutics for pathogen spread and evolution.

Host nutrition alters the variance in parasite transmission potential

The environmental conditions experienced by hosts are known to affect their mean parasite transmission potential. How different conditions may affect the variance of transmission potential has received less attention, but is an important question for disease management, especially if specific ecological contexts are more likely to foster a few extremely infectious hosts. Using the obligate-killing bacterium Pasteuria ramosa and its crustacean host Daphnia magna, we analysed how host nutrition affected the variance of individual parasite loads, and, therefore, transmission potential. Under low food, individual parasite loads showed similar mean and variance, following a Poisson distribution. By contrast, among well-nourished hosts, parasite loads were right-skewed and overdispersed, following a negative binomial distribution. Abundant food may, therefore, yield individuals causing potentially more transmission than the population average. Measuring both the mean and variance of individual parasite loads in controlled experimental infections may offer a useful way of revealing risk factors for potential highly infectious hosts.

Fecundity compensation and tolerance to a sterilizing pathogen in Daphnia

Hosts are armed with several lines of defence in the battle against parasites: they may prevent the establishment of infection, reduce parasite growth once infected or persevere through mechanisms that reduce the damage caused by infection, called tolerance. Studies on tolerance in animals have focused on mortality, and sterility tolerance has not been investigated experimentally. Here, we tested for genetic variation in the multiple steps of defence when the invertebrate Daphnia magna is infected with the sterilizing bacterial pathogen Pasteuria ramosa: anti‐infection resistance, anti‐growth resistance and the ability to tolerate sterilization once infected. When exposed to nine doses of a genetically diverse pathogen inoculum, six host genotypes varied in their average susceptibility to infection and in their parasite loads once infected. How host fecundity changed with increasing parasite loads did not vary between genotypes, indicating that there was no genetic variation for this measure of fecundity tolerance. However, genotypes differed in their level of fecundity compensation under infection, and we discuss how, by increasing host fitness without targeting parasite densities, fecundity compensation is consistent with the functional definition of tolerance. Such infection‐induced life‐history shifts are not traditionally considered to be part of the immune response, but may crucially reduce harm (in terms of fitness loss) caused by disease, and are a distinct source of selection on pathogens.

Costs of CRISPR-Cas-mediated resistance in Streptococcus thermophilus

CRISPR-Cas is a form of adaptive sequence-specific immunity in microbes. This system offers unique opportunities for the study of coevolution between bacteria and their viral pathogens, bacteriophages. A full understanding of the coevolutionary dynamics of CRISPR-Cas requires knowing the magnitude of the cost of resisting infection. Here, using the gram-positive bacterium Streptococcus thermophilus and its associated virulent phage 2972, a well-established model system harbouring at least two type II functional CRISPR-Cas systems, we obtained different fitness measures based on growth assays in isolation or in pairwise competition. We measured the fitness cost associated with different components of this adaptive immune system: the cost of Cas protein expression, the constitutive cost of increasing immune memory through additional spacers, and the conditional costs of immunity during phage exposure. We found that Cas protein expression is particularly costly, as Cas-deficient mutants achieved higher competitive abilities than the wild-type strain with functional Cas proteins. Increasing immune memory by acquiring up to four phage-derived spacers was not associated with fitness costs. In addition, the activation of the CRISPR-Cas system during phage exposure induces significant but small fitness costs. Together these results suggest that the costs of the CRISPR-Cas system arise mainly due to the maintenance of the defence system. We discuss the implications of these results for the evolution of CRISPR-Cas-mediated immunity.

Successfully resisting a pathogen is rarely costly in Daphnia magna

BackgroundA central hypothesis in the evolutionary ecology of parasitism is that trade-offs exist between resistance to parasites and other fitness components such as fecundity, growth, survival, and predator avoidance, or resistance to other parasites. These trade-offs are called costs of resistance. These costs fall into two broad categories: constitutive costs of resistance, which arise from a negative genetic covariance between immunity and other fitness-related traits, and inducible costs of resistance, which are the physiological costs incurred by hosts when mounting an immune response. We sought to study inducible costs in depth using the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa.ResultsWe designed specific experiments to study the costs induced by exposure to this parasite, and we re-analysed previously published data in an effort to determine the generality of such costs. However, despite the variety of genetic backgrounds of both hosts and parasites, and the different exposure protocols and environmental conditions used in these experiment, this work showed that costs of exposure can only rarely be detected in the D. magna-P. ramosa system.ConclusionsWe discuss possible reasons for this lack of detectable costs, including scenarios where costs of resistance to parasites might not play a major role in the co-evolution of hosts and parasites.